The general objective of this research project is to utilize measuring techniques developed in our laboratory to study those changes in the basic cellular and membrane mechanisms underlying the extrinsic and intrinsic control of vascular smooth muscle (VSM) reactivity, contractility and integrity, that may be intimately involved, either primarily or secondarily in the pathogenesis of essential hypertension. We are specifically interested in establishing the sequential development and relative importance of alterations in 1) the inherent reactivity and contractility of VSM; 2) the active control of VSM tone and 3) blood vessel hypertrophy in the genesis of this circulatory disease state. Changes in VSM properties and variables controlling inherent VSM function that will be measured include: VSM membrane potential changes and electrical activity, ion activities (e.g. K ion, Na ion, Ca ions); VSM tissue and plasma concentrations of vasoactive humoral substances (e.g. epinephrine, norepinephrine, histamine, serotonin) and changes in small blood vessel dimensions in response to topical application or suffusion of these vasoactive agents. Electron and scanning microscopy will be used to study structural changes in the small blood vessels including their VSM and innervation. Measurements will be made using both in vivo experimental preparations of suffused small arterial and venous vessels (e.g. mesenteric, skeletal and cerebral vascular beds) and in vitro preparations of VSM strips from larger arteries (e.g. femoral, renal and carotid). The DCA - and spontaneously hypertensive rat will be used as experimental models of essential hypertension. When available, human tissue samples incident to surgical procedures will be utilized. It is anticipated that evaluation of this data will clarify the sequence and loci of the peripheral circulatory abnormality involved in the development of essential hypertension.